PUBLICATION
Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver
- Authors
- Singh, M.K., Jayarajan, R., Varshney, S., Upadrasta, S., Singh, A., Yadav, R., Scaria, V., Sengupta, S., Shanmugam, D., Shalimar, ., Sivasubbu, S., Gandotra, S., Sachidanandan, C.
- ID
- ZDB-PUB-210216-1
- Date
- 2021
- Source
- Biochimica et biophysica acta. Molecular and cell biology of lipids 1866(5): 158905 (Journal)
- Registered Authors
- Sachidanandan, Chetana, Sivasubbu, Sridhar
- Keywords
- DHAP, Interleukin 6, aldolase b, inflammation, lean NAFLD, non-alcoholic fatty liver
- MeSH Terms
-
- Animals
- Animals, Genetically Modified*/genetics
- Animals, Genetically Modified*/metabolism
- Glycolysis/genetics*
- Hep G2 Cells
- Humans
- Interleukin-6*/biosynthesis
- Interleukin-6*/genetics
- Lipid Metabolism/genetics*
- Liver/metabolism*
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 33582286 Full text @ BBA Molecular and Cell Biology of Lipids
Citation
Singh, M.K., Jayarajan, R., Varshney, S., Upadrasta, S., Singh, A., Yadav, R., Scaria, V., Sengupta, S., Shanmugam, D., Shalimar, ., Sivasubbu, S., Gandotra, S., Sachidanandan, C. (2021) Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver. Biochimica et biophysica acta. Molecular and cell biology of lipids. 1866(5):158905.
Abstract
Inflammation is a constant in Non-Alcoholic Fatty Liver Disease (NAFLD), although their relationship is unclear. In a transgenic zebrafish system with chronic systemic overexpression of human IL6 (IL6-OE) we show that inflammation can cause intra-hepatic accumulation of triglycerides. Transcriptomics and proteomics analysis of the IL6-OE liver revealed a deregulation of glycolysis/gluconeogenesis pathway, especially a striking down regulation of the glycolytic enzyme aldolase b. Metabolomics analysis by mass spectrometry showed accumulation of hexose monophosphates and their derivatives, which can act as precursors for triglyceride synthesis. Our results suggest that IL6-driven repression of glycolysis/gluconeogenesis, specifically aldolase b, may be a novel mechanism for fatty liver. This mechanism may be relevant for NAFLD in lean individuals, an emerging class of NAFLD prevalent more in Asian Indian populations.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping